進行 EGFR 遺伝子変異陽性非小細胞肺癌に対する免疫チェックポイント阻害薬を用いた治療の現状と展望

The therapeutic effect of immune checkpoint inhibitors as a single agent for advanced non-small cell lung cancer with EGFR mutations is limited, therefore, the development of treatments using immune checkpoint inhibitors has shifted to combination therapy with other drugs. Phase 3 trials (CheckMate 722 and KEYNOTE-789) were conducted to investigate the addition of an immune checkpoint inhibitor to platinum-based chemotherapy in patients with advanced non-small cell lung cancer with EGFR mutations that had become resistant to EGFR-TKIs. Progression-free survival/overall survival tended to be extended with the addition of an immune checkpoint inhibitor in both trials. However, the benefits were not statistically significant and the treatment was not approved. On the other hand, in the IMpower150 study and the Japanese APPLE (WJOG11218L) study, bevacizumab, an anti-angiogenic agent, plus platinum-based chemotherapy in combination with an immune checkpoint inhibitor resulted in favorable outcomes for patients with EGFR mutated advanced non-small cell lung cancer. Furthermore, in the phase 3 trials (ATTLAS and ORIENT-31) conducted in South Korea and China, respectively, platinum-based chemotherapy plus an immune checkpoint inhibitor plus an anti-angiogenic agent was demonstrated to significantly prolong progression-free survival relative to platinum-based chemotherapy in patients with advanced EGFR mutation-positive non-small cell lung cancer that had become resistant to EGFR-TKIs. Based on evidence accumulated in recent clinical trials, platinum-based chemotherapy combined with an immune checkpoint inhibitor and an anti-angiogenic agent is an important treatment option for advanced non-small cell lung cancer with EGFR mutations that is refractory to EGFR-TKI.